Bleeding into the vitreous can occur as a result of many diseases or injuries. This proposal aims to examine the changes in vitreous cells and matrix as the tissue responds to hemorrhagic injury. As a result of experimental hemorrhage, the vitreous is invaded by phagocytic cells. Experiments to investigate the involvement of these cells in proliferative and degradative events are proposed. Of particular interest is to determine the role of these cells in matrix changes leading to vitreal liquefaction; that is, to determine if the phagocytic cells release free radicals or enzymes likely to degrade vitreous matrix macromolecules. In some extraretinopathic conditions the vitreous contains strands consisting of retinal glial or pigmented epithelial cells surrounded by a compact matrix that can obscure vision. Vitreous hemorrhage may stimulate the formation of dense strands and promote conditions causing tractional detachment of the retina. In this proposal experiments are planned to examine components of blood, or the vitreous response to blood, that stimulate proliferation or matrix synthesis by the invasive retinal cells. The investigation aims to determine if invasive cells deposit matrix components, like collagen, that differ from the types normally found in vitreous and if matrix secretion is altered in type or amount by vitreous hemorrhage. A major goal of the proposed project is to develop a comprehensive view of the vitreous response to hemorrhage in terms of the sequence of changes in cell populations, and in anabolic and catabolic processes.